Novel, potent P²–P³ pyrrolidine derivatives of ketoamide-based cathepsin K inhibitors

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• 作者：David G. Barrett ; John G. Catalano ; David N. Deaton ; Anne M. Hassell ; Stacey T. Long ; Aaron B. Miller ; Larry R. Miller ; John A. Ray ; Vicente Samano ; Lisa M. Shewchuk et al.
• 关键词：Cathepsin K ; Inhibitor ; Osteoporosis ; Ketoamide ; Synthesis
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2006
• 出版时间：15 March 2006
• 年：2006
• 卷：16
• 期：6
• 页码：1735-1739
• 全文大小：205 K

文摘

Starting from a potent pantolactone ketoamide cathepsin K inhibitor discovered from structural screening, conversion of the lactone scaffold to a pyrrolidine scaffold allowed exploration of the S³ subsite of cathepsin K. Manipulation of P³ and me=""mml2"">method=retrieve&_udi=B6TF9-4J14P1K-7&_mathId=mml2&_user=10&_cdi=5221&_rdoc=59&_handle=V-WA-A-W-ZC-MsSAYWA-UUA-U-AAVCVBZWCB-AAVBUADUCB-DBZZBDEEC-ZC-U&_acct=C000050221&_version=1&_userid=10&md5=3b7fc6b9ed15b00eeebea8334b8f8f58"" title=""Click to view the MathML source"">P^1′ groups afforded potent inhibitors with drug-like properties.